Fabrication of heparinized hierarchically hollow hydroxyapatite microspheres as bone substitute for controlled growth factors delivery

Abstract

Heparin-functionalized hollow hydroxyapatite microspheres were successfully prepared using heparin-entrapped calcium carbonate particles as original materials in a Na₂HPO₄-containing emulsion system. Heparin plays an important role in the formation of hollow structures. The obtained microspheres exhibit good anticoagulant ability and sustained release of basic fibroblast growth factor (bFGF). The cell viability assays indicate that the microspheres are nearly non-toxic to mouse embryo fibroblasts (MEFs) cells up to a concentration of 200 μg mL⁻¹, and the proliferation activity of the bFGF-loaded microspheres could be prolonged to at least 6 days. The simulated body fluid immersion tests reveal that the microspheres have a good in vitro bioactivity. Our results suggest that the obtained microspheres may serve as promising candidates for simultaneous use as bone reconstruction material and growth factors delivery vehicle.